Strong hyperconjugative interactions limit solvent and substituent influence on conformational equilibrium: the case of cis-2-halocyclohexylamines.

The presence of strong stereoelectronic interactions involving the substituents in cis-2-substituted cyclohexanes may lead to results different from those expected. In this work, we studied the conformational behavior of cis-2-fluoro- (F), cis-2-chloro- (Cl), cis-2-bromo- (Br) and cis-2-iodocyclohexylamine (I) by dynamic NMR and theoretical calculations. The experimental data pointed to an equilibrium strongly shifted toward the ea conformer (equatorial amine group and axial halogen), with populations greater than 90% for F, Cl and Br in both dichloromethane-d 2 and methanol-d 4. Theoretical calculations (M06-2X/6-311++G(2df,2p)) were in agreement with the experimental, with no influence of the solvent or the halogen on the equilibrium. A principal component analysis of natural bond orbital energies pointed to the σ*C-X and σC-H orbitals and the halogen lone pairs (LPX) as the most significant for the hyperconjugative interactions that influenced the equilibrium. The σC-H → σ*C-X hyperconjugation and the interactions involving the LPX counterbalance each other, explaining the non-influence of the halogen on the conformational equilibrium. These interactions are responsible for the strong preference for the ea conformer in cis-2-halocyclohexylamines, being strong enough to restrain the shift in the equilibrium due to other factors such as steric repulsion or solvent effects.

Structural Characterization and Biological Evaluation of 18-Nor-ent-labdane Diterpenoids from Grazielia gaudichaudeana.

The phytochemical investigation of Grazielia gaudichaudeana aerial parts yielded 15 compounds, including diterpenes, triterpenes, sterols and flavonoids. With exception to ent-kaurenoic acid diterpenes, the compounds isolated are being described for the first time in this species. Some unusual 1 H-NMR chemical shifts of 18-nor-ent-labdane (7-9) led us carry out a conformational analysis by theoretical calculations in order to support the experimental data. Moreover, due to the limitation of studies focused on pharmacological potential of Grazielia gaudichaudeana, the present study was carried out to investigate the antioxidant, antiproliferative, antiviral, antileishmanial and antimicrobial activities from the extract, fractions and isolated compounds obtained from this species. Ethyl acetate fraction showed significant activity in the antiproliferative assay, with GI50 range of 3.9 to 27.2 µg mL-1 . Dichloromethane fraction, rich in diterpenoids, inhibited all human tumor cell lines tested, and the nor-labdane 7 showed potent cytotoxic activity against glioma and ovary cancer cell lines.

Antimicrobial and Antioxidant Activities of the Extract and Fractions of Tetradenia riparia (Hochst.) Codd (Lamiaceae) Leaves from Brazil.

Tetradenia riparia (Lamiaceae) is native to Central Africa popularly known as myrrh, used in folk medicine to treat various diseases like malaria, gastroenteritis, and tropical skin disease. This research was to evaluate the antioxidant and antibacterial activities of the crude extract (CE) and fractions (FR) of the T. riparia by classical chromatography. The CE of T. riparia leaves was submitted to column chromatographic fractionation to obtain four fractions of the interest, which were identified by nuclear magnetic resonance and gas chromatograph coupled to mass spectrum: FR-I (abieta-7,9(11)-dien-13-ß-ol), FR-II (Ibozol), FR-III (8 (14), 15-sandaracopimaradiene-2α, 18-diol and 8 (14), 15-sandaracopimaradiene-7α, 18-diol), and FR-IV (Astragalin, Boronolide and Luteolin). Total phenol content of CE and FR were measured, and antioxidant action by methods of DPPH (2,2-diphenyl-1-picrylhydrazyl), ß-carotene/linoleic acid system, and ferric reducing/antioxidant power (FRAP) and the antibacterial activity was evaluated by the broth microdilution method with the determination of the minimum inhibitory concentration (MIC). The FR-IV presented antioxidant potential with 181.67 µg gallic acid/mg, IC50 of 0.61 µg/mL by DPPH method, 55.61% oxidation protection by ß-carotene/linoleic acid system and 4.59 µM ferrous sulfate/mg of sample by FRAP, and the FR-I showed higher antibacterial potential on the strain Staphylococcus aureus with MIC 0.98 µg/mL, Enterococcus faecalis and Bacillus cereus with MIC 31.2 µg/mL. Thus, the fractionation of CE was extremely important to detect fractions with potential activities, and investigations are necessary regarding the mechanism of action and action in vivo.

Conformational equilibrium of phenylacetic acid and its halogenated analogues through theoretical studies, NMR and IR spectroscopy.

This paper presents a study on the conformational preferences of phenylacetic acid (PA) and its halogenated analogues (FPA, CPA, BPA). To clarify the effects that rule these molecules' behaviour, theoretical calculations were used, for both the isolated phase and solution, combined with nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy. Most conformations of phenylacetic acid and its halogenated derivatives are stabilized through the hyperconjugative effect, which rules the conformational preference. NMR analyses showed that even with the variation in medium polarity, there was no significant change in the conformation population. Infrared spectroscopy showed similar results for all compounds under study. In most spectra, two bands were found through the carbonyl deconvolution, which is in accordance with the theoretical data. It was possible to prove that variation in the nature of the substituent in the ortho position had no significant influence on the conformational equilibrium.